Preparation, Solid-State Characterization, Phase Solubility and Dissolution Studies of Azithromycin/Hydroxypropyl-β- Cyclodextrin Host-Guest System

Abstract

Objectives: Azithromycin has poor aqueous solubility and its dissolution is the rate-limiting step. Therefore the objective of this work to increase the solubility and dissolution of azithromycin. Hence aim of the study was to develop, characterize and evaluate dissolution properties of inclusion complexes of Azithromycin with hydroxypropyl-β-cyclodextrin (HP-β-CD).Methods: Phase solubility was performed by Higuchi and Connors’s meth- od for determination of stoichiometry of AZM/ β-CD and AZM/ HP-β-CD inclusion complex. It again confirmed by Jobs plot. Inclusion complex of Azithromycin with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by kneading method and solvent evaporation method in molar ratio of 1:1. The inclusion complex in solid state was characterized by FT-IR, DSC, HNMR, SEM.Results: AL type was found in the phase solubility diagram which indicated the development of the inclusion complex in 1:1 stoichiometry with HP-β-CD. The stability constant decrease with increasing temperature. All thermodynamic parameters for the inclusion complex were calculated from Van’t Hoff plots. The highest enhancement in dissolution and solubil- ity were observed in the inclusion complex developed with HPβ-CD using the kneading method. FT-IR spectra exhibited that the hydroxyl group of azithromycin was participate in inclusion process. DSC study supported amorphization of drug molecule and entrapment of drug in the HP-β-CD cavity. It further confirmed with nuclear magnetic resonance and scanning electron microscopy studies.Conclusion: The solubility was significantly improved by the inclusion complex with HP-β-CD (9 fold). The dissolution of azithromycin was improved with inclusion phenomena using kneading method. The result of studies showed the inclusion of Azithromycin mol- ecule inside HP-β-CD cavities.

Keywords: Azithromycin; Hydroxypropyl-β-cyclodextrin; Inclusion complex; Kneading method